ABSTRACT Over 20 million US adults and youth suffer from substance use disorders (SUDs) and substance use (SU) related problems. However, most people with SUDs never receive SUD treatment. Historically, research on SUDs has focused on the small minority of patients with SUDs who are seeking, or already engaged in, specialty SUD treatment. The overall goal of the proposed Addictions Research Network (ARN) node of the Clinical Trials Network will be to conduct cutting edge research to improve outcomes in all patients with SU/SUD who are seen in medical settings. The ARN includes 15 large health systems across the US that use the HMO Research Network?s (HMORN?s) Virtual Data Warehouse, providing geographic and racial/ethnic diversity as well as variation in systems of medical and SU/SUD care. The proposed ARN node has 3 broad agendas?1) to evaluate effective practices for identifying, engaging and treating patients with SU or SUDs in medical settings; 2) to develop and test effective, practical ways to implement these practices in a sustained manner as part of routine medical care; and 3) to develop and disseminate innovative research methods on SU and SUDs. Three PIs will lead the ARN node, each with expertise critical to our research agenda. Dr. Weisner, who has more than 25 years of experience leading SUD research in public and private medical settings, will lead the ARN as Senior PI at Kaiser Permanente. She partners at Kaiser Permanente with Dr. Campbell, an expert in research on opioid misuse and patient-centered and comparative effectiveness research, and Dr. Bradley, Senior PI at Group Health, who has 20 years of research experience targeting non-treatment-seeking patients with alcohol misuse and SUDs in medical settings. The ARN will have 3 Cores: 1) an Administrative Core will support all aspects of the ARN node; 2) an Implementation Core will support patient-centered design of practical, sustainable approaches to implementing SUD care in routine medical settings using electronic health records (EHRs), and; 3) an Analytics Core with expertise in programming, biostatistics using EHR data, and economics, will support innovative methods research and study design. ARN work will leverage the HMORN?s 20 years of conducting pragmatic clinical trials and comparative effectiveness research across health systems using EHRs and the nationwide Virtual Data Warehouse. The ARN node will provide a robust foundation for population-based studies?including pragmatic randomized controlled trials, comparative effectiveness studies, and implementation research?that can evaluate long-term health outcomes. Moreover, through our connection to 15 learning healthcare systems, our research will design approaches to improve the quality of care for SU and SUDs in real-world medical settings. In this way?with the other CTN nodes?the ARN node will help build the infrastructure required for the next era of addictions health services research.